Breast cancer incidence and mortality are much higher in industrialized societies than in developing societies, and the reasons for these differences are not well understood. The search for aspects of modern life that increase risk has been intense but of limited success. "Circadian Disruption" may play a role. The overall goal is to develop an interdisciplinary scientific team and program of research on the topic of circadian disruption, primarily from alterations in lighting, as it might influence risk of breast cancer. Integral to this effort is targeted utilization of the Environmental Genome to find candidate genes which may modify human physiological response to "circadian disruptors" such as altered lighting. This effort will begin with investigation of CLOCK genes and genes affecting circadian phototransduction. The researchers intend to establish a multidisciplinary collaboration among molecular, developmental, and circadian biologists; statisticians and epidemiologists to develop a better understanding of the impact of light on breast cancer induction and the role that genetic polymorphisms may play in this. In order to initiate this collaboration, a 3-day retreat will be conducted early in the first year of the project period. From this, priorities will be discussed and focused pilot projects planned. The principal investigator will ensure regular communication among study collaborators as the project progresses. There will also be a meeting in each of years 2 and 3 of the project. In addition, the investigators will translate the insight gained above into markers for use in epidemiological studies of light and breast cancer that are relevant to the biological mechanisms involved and at the same time efficient for use in the large numbers of women necessary to provide meaningful data. Results of theoretical work among combinations of the participants, and of the experiments conducted, will be published. A final summary document will be prepared by the end of the third year with input from all collaborators. Most of the researchers in this proposal participated in a conference at NIH in March, 2000 entitled "Circadian Disruption as Endocrine Disruption in Breast Cancer." This conference was covered in a NEWS article in the May 3, 2000 issue of journal of the National Cancer Institute which is archived on the web at: http://jnci.oupjoumals.org/cgi/content/full/92/9/686. It represents the investigators' initial efforts at crossdiscipline collaboration on the emerging topic of lighting, circadian disruption, and breast cancer.